Sawyer J R, Swanson C M, Wheeler G, Cunniff C
Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock 72202, USA.
Am J Med Genet. 1995 Mar 27;56(2):203-9. doi: 10.1002/ajmg.1320560218.
We report on a new patient with immunodeficiency, centromeric heterochromatin instability, and facial anomalies (the ICF syndrome). Studies with traditional cytogenetic methods demonstrate that aberrations in this syndrome primarily involve the centromeric regions of chromosomes 1 and 16. We applied fluorescence in situ hybridization (FISH) using "painting" probes for chromosomes 1 and 16 to document the progression of centromeric instability from simple decondensation aberrations to the subsequent formation of complex multibranched chromosomes 1, and finally to the interphase aberrations of nuclear projections and micronuclei involving both chromosomes 1 and 16. The loss of the large multibranched chromosome 1 configurations from the cells as micronuclei suggests that the centromeric aberrations subsequently interfere with normal chromosome movement at anaphase in ICF syndrome. Circular areas of counterstained chromatin were observed by FISH in the micronuclei corresponding to the intertwined segments of centromeric heterochromatin seen involving multibranched chromosomes 1 in the patient's G-banded chromosome study. The current hypothesis of recessive inheritance for this disorder suggests that the chromosomal aberrations are not a causative event in this syndrome; however, the chromosome aberrations are clearly an important basic diagnostic criterion.
我们报告了一例患有免疫缺陷、着丝粒异染色质不稳定和面部异常（ICF综合征）的新患者。采用传统细胞遗传学方法进行的研究表明，该综合征中的畸变主要涉及1号和16号染色体的着丝粒区域。我们应用针对1号和16号染色体的“涂抹”探针进行荧光原位杂交（FISH），以记录着丝粒不稳定从简单的解聚畸变到随后形成复杂的多分支1号染色体，最终到涉及1号和16号染色体的核突出物和微核的间期畸变的进展过程。作为微核从细胞中丢失的大型多分支1号染色体构型表明，着丝粒畸变随后在ICF综合征的后期干扰了正常染色体移动。通过FISH在微核中观察到反染染色质的圆形区域，这与在患者的G带染色体研究中涉及多分支1号染色体的着丝粒异染色质的交织片段相对应。关于该疾病隐性遗传的当前假说表明，染色体畸变在该综合征中并非致病事件；然而，染色体畸变显然是一项重要的基本诊断标准。
